Project Summary Compelling genetic, biochemical, cell biological, animal model, and human studies suggest that cerebral accumulation of the ?-amyloid peptide (A?) has a critical early role in Alzheimer's disease (AD) pathogenesis. The ?-secretase enzyme BACE1 is the rate-limiting enzyme for A? production. Thus, BACE1 is a prime therapeutic target for the treatment or prevention of AD. Several BACE1 inhibitor drugs for AD are in clinical trials, but the safety and efficacy of these agents are unknown. The BACE proteases field comprises very active and diverse areas of research that have high impact on therapeutic approaches to treat and prevent AD. Here, I propose the 2nd Kloster Seeon Meeting on BACE Proteases in Health and Disease, September 25-27, 2016, in Bavaria, Germany, which has the following objectives: 1) disseminate the latest information on BACE proteases research and catalyze discussion among scientists in academia and industry, 2) promote the training of young scientists, and 3) publish a state-of-the-art review of BACE research to help advance the field and facilitate the development of safe and effective BACE inhibitor drugs for AD. The Scientific Program consists of: 1) a Keynote Lecture by Dr. Kari Stefansson (DeCode Genetics), who recently discovered a mutation in APP that protects against AD by reducing BACE1 cleavage, thus providing proof of concept for therapeutic BACE1 inhibition, 2) two full days of sessions comprising 25-minute talks from 24 leading experts in the BACE proteases field, 3) a session of 2-minute flash talks given by 10 selected graduate students and post-doctoral researchers to introduce their posters, 4) poster sessions on each of two evenings that will enhance the training experience of students and post-docs, 5) a panel discussion between academic and industry scientists on the current state of BACE research and drug development, 6) a conclusion and summary session to remark on the meeting and discuss the direction forward for the field. This meeting is co-organized by Drs. Stefan Lichtenthaler (Technical University Munich) and Robert Vassar (Northwestern University), two leading scientists in the BACE proteases field. The 1st Kloster Seeon Meeting on BACE Proteases in Health and Disease was held at the same location on October 6-8, 2013, and was objectively successful at disseminating the latest BACE research and catalyzing discussion among BACE scientists. Three years have passed, and significant advances in BACE research have been made, including new clinical trials, discoveries of novel BACE1 substrates and functions, different mechanisms of BACE regulation in health and dysregulation in AD, and identification of new proteolytic activities. Given these new advances, the 2nd Kloster Seeon Meeting on BACE Proteases in Health and Disease is timely and important for dissemination of the latest information in the field. Additionally, no other scientific meeting or conference focuses exclusively on BACE proteases research, making this meeting a unique scientific forum that will contribute significantly to the advancement of the AD research and drug development fields.